Cell replacement and regeneration therapy for diabetes

Abstract

Reduction of beta cell function and a beta cell mass is observed in both type 1 and type 2 diabetes. Therefore, restoration of this deficiency might be a therapeutic option for treatment of diabetes. Islet transplantation has benefits, such as reduced incidence of hypoglycemia and achievement of insulin independence. However, the major drawback is an insufficient supply of islet donors. Transplantation of cells differentiated in vitro or in vivo regeneration of insulin-producing cells are possible approaches for beta cell/islet regenerative therapy. Embryonic and adult stem cells, pancreatic ductal progenitor cells, acinar cells, and other endocrine cells have been shown to differentiate into pancreatic beta cells. Formation of fully functional beta cells and the safety of these cells are critical issues for successful clinical application.

Keywords: Beta cell; Diabetes mellitus; Differentiation; Islets of Langerhans; Regeneration; Stem cells.

Fig. 1

Possible strategies for beta cell replacement and regeneration therapy. Insulin-producing cells can be restored by transplantation of cells derived from in vitro or in vivo regeneration. Transplantation of islets from normal subjects, insulin-producing cells differentiated from stem and/or progenitor cells in vitro, or non-β cells (e.g., hepatocytes) engineered to produce insulin can result in insulin production and control blood glucose levels. Introduction of stem cells, β cell growth factors or stimulation of β cell differentiation transcription factors can regenerate β cells in vivo, which then produce insulin and control blood glucose levels.